Speciality
Spotlight

 




 


Endocrinology


   

  




Lipoprotiens
and Atherosclerosis


   

  • HD White, RJ
    Simes, NE Anderson, et al (Univ. of Auckland, New Zealand; Univ.of Sydney, Australia; Royal Perth Hosp, Australia; et al )

    Pravastatin Therapy and the Risk of Stroke

    N Engl J Med 343: 317-326, 2000

        


    The effects of pravastatin on mortality were compared with placebo in a double-blind trial of 9014 patients, who had a history of myocardial infarction and unstable angina and a total cholesterol level of 155 to 271
    mg/dL.

       


    The authors concluded that pravastatin had a moderate impact in decreasing the risk of stroke from any cause and the risk of
    non-haemorrhagic stroke in patients with previous myocardial infarction or unstable
    angina.

       

  • M.J. Zema, (Brookhaven Mem Hosp Med Ctr, Patchogue, NY: State Univ of New York, Stony Brook)

    Gemfibrozil, Nicotinic Acid and Combination Therapy in Patients with Isolated Hypoalphalipoproteinema: A Randomized, Open-Label, Cross-over Study.


    J Am Coll Cardiol 35: 640-646, 2000


         

    This prospective, randomized, open-label cross-over trial was carried out on 23 patients to evaluate the effects of nicotinic acid (NA), gemfibrozil and combination therapy on the lipid profile of patients with clinical atherosclerotic disease and isolated hypoalphalipoproteinemia (low HDL cholesterol [HDL-C]).

        


    Pharmacologic therapy to increase HDL-C is possible and effective with currently available agents, especially when used in combination.

         


    In this study, triglycerides were not a therapeutic target because no patient had triglycerides more than 200mg/dL.

         


    Statin therapy achieves a better reduction in LDL-C than either gem fibrozil or NA. NA is more effective than a statin in increasing
    HDL-C.

           

  • S. Behar, for the BIP Study Group (Sheba Medical Centre, Tel-Hashomer, Israel; et al)

    Secondary Prevention by Raising HDL Cholesterol and Reducing Triglycerides in Patients with Coronary Artery Disease: The Bezafibrate Infarction Prevention (BIP) Study.


    Circulation : 102: 21-27, 2000

          



    The Bezafibrate Infarction Prevention (BIP) trial, a double-blind trial of 3090 patients with CAD (Coronary Artery Disease), evaluated whether bezafibrate which raises HDL-C and decreases triglycerides reduced CAD mortality and non-fatal myocardial infarction (MI).

          


    Bezafibrate was found to be safe and effective in raising HDL-C levels and lowering
    triglycerides.

          

  • DM Herrington, DM Reboussin, et al (Wake Forest Univ, Winston-Salem, NC; Carolinas Med Ctr, Charlotte, NC; Le Bauer Cardiovascular Associates, Greensboro, NC; et al)

    Effects of Estrogen Replacement on the Progression of Coronary-Artery Atherosclerosis.

    N Engl J Med 343: 522-529, 2000

          



    The authors found that for postmenopausal women with coronary atherosclerosis, oestrogen replacement therapy does not appear to influence the rate of atherosclerotic progression.

        


    Estrogen replacement may still be effective in primary prevention of coronary disease, but this needs to be confirmed.

        

  • Shlipak MG, Simon JA, Vittinghoff E, et al (Univ of California, San Francisco; Univ of California, San Diego; Univ of Washington, Seattle; et al) 

    Estrogen and Progestin, Lipoprotein(a), and the Risk of Recurrent Coronary Heart Disease Events After Menopause

    JAMA 283: 1845-1852, 2000

         

    Lipoprotein(a) (Lp(a)) has been identified as an independent risk factor for coronary heart disease (CHD) in men. Hormone replacement therapy (HRT) has been shown to lower Lp(a) levels in postmenopausal women.

         

    This randomized, blinded, placebo-controlled study was done to determine the relationships between HRT, serum Lp(a) levels and CHD in postmenopausal women.

        

    It was found that Lp(a) level appears to be an independent modifiable CHD risk factor in postmenopausal women. HRT appears to lower Lp(a) levels in these patients, and the cardiovascular benefits appear to be maximum in women with highest Lp(a) levels.

        

  • Blair SN, Capuzzi DM, Gottlieb SO, et al (Cooper Inst, Dallas; Jefferson Med College, Philadelphia; Midatlantic Cardiovascular Associates, Baltimore, Md; et al)

    Incremental Reduction of Serum Total Cholesterol and Low-Density Lipoprotein Cholesterol With the Addition of Plant Stanol Ester-Containing Spread to Statin Therapy 

    Am J Cardiol 86: 46-52, 2000

        

    Plant stanols effectively lower serum LDL-C levels. The authors studied the effects of combined therapy of a statin and a spread containing plant stanol esters in lowering serum levels of total cholesterol and LDL-C cholesterol.

         

    Consumption of a canola oil-based spread (providing 5.1 g per day of plant stanol) was effective in reducing both serum total cholesterol and LDL-C concentration in patients receiving a stable regimen of statin therapy.

         

    Concentrations of either serum triglycerides or HDL-C remained unaffected by this therapy.

          

  • Rask-Nissila L, Jokinen E, Terho P, et al (Univ of Turku, Finland; Univ of Helsinki)

    Neurological Development of 5-Year-Old Children Receiving a Low-Saturated Fat, Low-Cholesterol Diet Since Infancy: A Randomized Controlled Trial 

    JAMA 284: 993-1000, 2000

         

    The effects of a diet low in saturated fat and cholesterol on children’s neurologic development were investigated in a randomized controlled trial focussed on 1062, 7-month old infants and their parents seen at the well-baby clinics.

        

    A 3% to 5% reduction in serum cholesterol concentration may be achieved by nutritional intervention in the form of a low saturated-fat, low cholesterol diet begun early in life.

        

    This diet has no adverse effects on the neurologic development of these children.

         

  • Vakkilainen J, Makimattila S, Seppala-Lindroos A, et al (Helsinki Univ)

    Endothelial Dysfunction in Men With Small LDL Particles

    Circulation 102: 716-721, 2000

        

    Small, dense LDL particles may be more atherogenic than larger particles, showing decreased binding to LDL receptors and increased binding to the arterial wall. 

        

    In vivo endothelial function was evaluated through forearm blood flow response to acetylcholine (ACh) and sodium nitroprusside infusions in 34 healthy men.

        

    Gradient gel electrophoresis was used to measure LDL peak particle size and the euglycemic hyperinsulinemic clamp technique to determine the whole-body insulin sensitivity. 

        

    The authors conclude that small dense LDL particles are oxidized more easily and bind with greater affinity to arterial wall proteoglycans and receptor-independent cell surface binding sites. 

        

    Hence they contribute to endothelial dysfunction which may precede atherosclerosis and coronary artery disease.

         

  • Wolozin B, Kellman W, Ruosseau P, et al (Loyola Univ, Maywood, III; Edward Hines Jr Veterans Affairs Hosp, Hines, III; Carl T Hayden Veterans Affairs Med Ctr, Phoenix, Ariz)

    Decreased Prevalence of Alzheimer Disease Associated With 3-Hydroxy-3-Methyglutaryl Coenzyme A Reductase Inhibitors

    Arch Neurol 57: 1439-1443, 2000

         

    This study was from hospital records of 3 groups of patients who were receiving statins (lovastatin, simvastatin, or pravastatin) and patients taking medications to treat hypertension or cardiovascular diseases. Patients were aged 60 or above.

         

    It was found that lovastatin and pravastatin have a protective effect against Alzheimer’s disease. Simvastatin though chemically similar had no protective
    effect.

          

  • Agerholm-Larsen B, Nordestgaard BG, Steffenson R, et al (Univ of Copenhagen)

    Elevated HDL Cholesterol Is a Risk Factor For Ischemic Heart Disease in White Women When Caused by a Common Mutation in the Cholesteryl Ester Transfer Protein
    Gene
    .

    Circulation 101: 1907-1912, 2000

           


    Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to triglyceride-rich lipoproteins, which stimulates reverse cholesterol transport (from peripheral cells to the liver for excretion)

           


    A genetic deficiency of CETP is related to rises in HDL cholesterol (HDL-C) levels in homozygotes and to a lesser extent in heterozygotes.

           


    The effect of mutation in CETP on lipid, lipoprotein and apolipoprotein levels and on the risk of ischemic heart disease (IHD) was studied in 5069 women and 4099 men from a general white population sample and in 946 patients with IHD.

         


    The authors conclude that the clinical use of total to HDL-C as a risk indicator may be misleading in individuals with CETP mutations.

         

  • Kris-Etherton PM, Pearson TA, Wan Y, et al (Pennsylvania State Univ, Univ Park; Univ. of Rochester, NY)

    High-Monounsaturated Fatty Acid Diets Lower Both Plasma Cholesterol and Triacylglycerol Concentrations.

    Am J Clin Nutr 70: 1009-1015, 1999

          


    Low-fat diets raise plasma triacylglycerol and reduce HDL-cholesterol (HDL-C) concentrations, potentially adversely affecting cardiovascular disease
    (CVD), risk.


          


    High-monounsaturated fatty acid (MUFA) diet, is an alternative diet where saturated fats are replaced by MUFA.

         


    A randomized, double-blind. 5-period crossover study design was used to ascertain the effects of different diets on serum lipids and lipoproteins.

           


    A high-MUFA, cholesterol-lowering diet may be preferred to a low-fat diet, with favourable effects on CVD risk profile.

        



 

 

Speciality Spotlight

 

 
Endocrinology
   

  

Lipoprotiens and Atherosclerosis
   

  • HD White, RJ Simes, NE Anderson, et al (Univ. of Auckland, New Zealand; Univ.of Sydney, Australia; Royal Perth Hosp, Australia; et al )
    Pravastatin Therapy and the Risk of Stroke
    N Engl J Med 343: 317-326, 2000
        
    The effects of pravastatin on mortality were compared with placebo in a double-blind trial of 9014 patients, who had a history of myocardial infarction and unstable angina and a total cholesterol level of 155 to 271 mg/dL.
       
    The authors concluded that pravastatin had a moderate impact in decreasing the risk of stroke from any cause and the risk of non-haemorrhagic stroke in patients with previous myocardial infarction or unstable angina.
       

  • M.J. Zema, (Brookhaven Mem Hosp Med Ctr, Patchogue, NY: State Univ of New York, Stony Brook)
    Gemfibrozil, Nicotinic Acid and Combination Therapy in Patients with Isolated Hypoalphalipoproteinema: A Randomized, Open-Label, Cross-over Study.
    J Am Coll Cardiol 35: 640-646, 2000
         
    This prospective, randomized, open-label cross-over trial was carried out on 23 patients to evaluate the effects of nicotinic acid (NA), gemfibrozil and combination therapy on the lipid profile of patients with clinical atherosclerotic disease and isolated hypoalphalipoproteinemia (low HDL cholesterol [HDL-C]).
        
    Pharmacologic therapy to increase HDL-C is possible and effective with currently available agents, especially when used in combination.
         
    In this study, triglycerides were not a therapeutic target because no patient had triglycerides more than 200mg/dL.
         
    Statin therapy achieves a better reduction in LDL-C than either gem fibrozil or NA. NA is more effective than a statin in increasing HDL-C.
           

  • S. Behar, for the BIP Study Group (Sheba Medical Centre, Tel-Hashomer, Israel; et al)
    Secondary Prevention by Raising HDL Cholesterol and Reducing Triglycerides in Patients with Coronary Artery Disease: The Bezafibrate Infarction Prevention (BIP) Study.
    Circulation : 102: 21-27, 2000
          

    The Bezafibrate Infarction Prevention (BIP) trial, a double-blind trial of 3090 patients with CAD (Coronary Artery Disease), evaluated whether bezafibrate which raises HDL-C and decreases triglycerides reduced CAD mortality and non-fatal myocardial infarction (MI).
          
    Bezafibrate was found to be safe and effective in raising HDL-C levels and lowering triglycerides.
          

  • DM Herrington, DM Reboussin, et al (Wake Forest Univ, Winston-Salem, NC; Carolinas Med Ctr, Charlotte, NC; Le Bauer Cardiovascular Associates, Greensboro, NC; et al)
    Effects of Estrogen Replacement on the Progression of Coronary-Artery Atherosclerosis.
    N Engl J Med 343: 522-529, 2000
          

    The authors found that for postmenopausal women with coronary atherosclerosis, oestrogen replacement therapy does not appear to influence the rate of atherosclerotic progression.
        
    Estrogen replacement may still be effective in primary prevention of coronary disease, but this needs to be confirmed.
        

  • Shlipak MG, Simon JA, Vittinghoff E, et al (Univ of California, San Francisco; Univ of California, San Diego; Univ of Washington, Seattle; et al) 
    Estrogen and Progestin, Lipoprotein(a), and the Risk of Recurrent Coronary Heart Disease Events After Menopause
    JAMA 283: 1845-1852, 2000
         
    Lipoprotein(a) (Lp(a)) has been identified as an independent risk factor for coronary heart disease (CHD) in men. Hormone replacement therapy (HRT) has been shown to lower Lp(a) levels in postmenopausal women.
         
    This randomized, blinded, placebo-controlled study was done to determine the relationships between HRT, serum Lp(a) levels and CHD in postmenopausal women.
        
    It was found that Lp(a) level appears to be an independent modifiable CHD risk factor in postmenopausal women. HRT appears to lower Lp(a) levels in these patients, and the cardiovascular benefits appear to be maximum in women with highest Lp(a) levels.
        

  • Blair SN, Capuzzi DM, Gottlieb SO, et al (Cooper Inst, Dallas; Jefferson Med College, Philadelphia; Midatlantic Cardiovascular Associates, Baltimore, Md; et al)
    Incremental Reduction of Serum Total Cholesterol and Low-Density Lipoprotein Cholesterol With the Addition of Plant Stanol Ester-Containing Spread to Statin Therapy 
    Am J Cardiol 86: 46-52, 2000
        
    Plant stanols effectively lower serum LDL-C levels. The authors studied the effects of combined therapy of a statin and a spread containing plant stanol esters in lowering serum levels of total cholesterol and LDL-C cholesterol.
         
    Consumption of a canola oil-based spread (providing 5.1 g per day of plant stanol) was effective in reducing both serum total cholesterol and LDL-C concentration in patients receiving a stable regimen of statin therapy.
         
    Concentrations of either serum triglycerides or HDL-C remained unaffected by this therapy.
          

  • Rask-Nissila L, Jokinen E, Terho P, et al (Univ of Turku, Finland; Univ of Helsinki)
    Neurological Development of 5-Year-Old Children Receiving a Low-Saturated Fat, Low-Cholesterol Diet Since Infancy: A Randomized Controlled Trial 
    JAMA 284: 993-1000, 2000
         
    The effects of a diet low in saturated fat and cholesterol on children’s neurologic development were investigated in a randomized controlled trial focussed on 1062, 7-month old infants and their parents seen at the well-baby clinics.
        
    A 3% to 5% reduction in serum cholesterol concentration may be achieved by nutritional intervention in the form of a low saturated-fat, low cholesterol diet begun early in life.
        
    This diet has no adverse effects on the neurologic development of these children.
         

  • Vakkilainen J, Makimattila S, Seppala-Lindroos A, et al (Helsinki Univ)
    Endothelial Dysfunction in Men With Small LDL Particles
    Circulation 102: 716-721, 2000
        
    Small, dense LDL particles may be more atherogenic than larger particles, showing decreased binding to LDL receptors and increased binding to the arterial wall. 
        
    In vivo endothelial function was evaluated through forearm blood flow response to acetylcholine (ACh) and sodium nitroprusside infusions in 34 healthy men.
        
    Gradient gel electrophoresis was used to measure LDL peak particle size and the euglycemic hyperinsulinemic clamp technique to determine the whole-body insulin sensitivity. 
        
    The authors conclude that small dense LDL particles are oxidized more easily and bind with greater affinity to arterial wall proteoglycans and receptor-independent cell surface binding sites. 
        
    Hence they contribute to endothelial dysfunction which may precede atherosclerosis and coronary artery disease.
         

  • Wolozin B, Kellman W, Ruosseau P, et al (Loyola Univ, Maywood, III; Edward Hines Jr Veterans Affairs Hosp, Hines, III; Carl T Hayden Veterans Affairs Med Ctr, Phoenix, Ariz)
    Decreased Prevalence of Alzheimer Disease Associated With 3-Hydroxy-3-Methyglutaryl Coenzyme A Reductase Inhibitors
    Arch Neurol 57: 1439-1443, 2000
         
    This study was from hospital records of 3 groups of patients who were receiving statins (lovastatin, simvastatin, or pravastatin) and patients taking medications to treat hypertension or cardiovascular diseases. Patients were aged 60 or above.
         
    It was found that lovastatin and pravastatin have a protective effect against Alzheimer’s disease. Simvastatin though chemically similar had no protective effect.
          

  • Agerholm-Larsen B, Nordestgaard BG, Steffenson R, et al (Univ of Copenhagen)
    Elevated HDL Cholesterol Is a Risk Factor For Ischemic Heart Disease in White Women When Caused by a Common Mutation in the Cholesteryl Ester Transfer Protein Gene.
    Circulation 101: 1907-1912, 2000
           
    Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to triglyceride-rich lipoproteins, which stimulates reverse cholesterol transport (from peripheral cells to the liver for excretion)
           
    A genetic deficiency of CETP is related to rises in HDL cholesterol (HDL-C) levels in homozygotes and to a lesser extent in heterozygotes.
           
    The effect of mutation in CETP on lipid, lipoprotein and apolipoprotein levels and on the risk of ischemic heart disease (IHD) was studied in 5069 women and 4099 men from a general white population sample and in 946 patients with IHD.
         
    The authors conclude that the clinical use of total to HDL-C as a risk indicator may be misleading in individuals with CETP mutations.
         

  • Kris-Etherton PM, Pearson TA, Wan Y, et al (Pennsylvania State Univ, Univ Park; Univ. of Rochester, NY)
    High-Monounsaturated Fatty Acid Diets Lower Both Plasma Cholesterol and Triacylglycerol Concentrations.
    Am J Clin Nutr 70: 1009-1015, 1999
          
    Low-fat diets raise plasma triacylglycerol and reduce HDL-cholesterol (HDL-C) concentrations, potentially adversely affecting cardiovascular disease (CVD), risk.
          
    High-monounsaturated fatty acid (MUFA) diet, is an alternative diet where saturated fats are replaced by MUFA.
         
    A randomized, double-blind. 5-period crossover study design was used to ascertain the effects of different diets on serum lipids and lipoproteins.
           
    A high-MUFA, cholesterol-lowering diet may be preferred to a low-fat diet, with favourable effects on CVD risk profile.
        

 

By |2022-07-20T16:41:06+00:00July 20, 2022|Uncategorized|Comments Off on Lipoproteins And Atherosclerosis

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